Nesprin interchain associations control nuclear size
Nesprin interchain associations control nuclear size
复制标题
DOI：
10.1007/s00018-012-1034-1
复制
发表时间：
2012-10-01
影响因子：
8
通讯作者：
Karakesisoglou, Iakowos
中科院分区：
文献类型：
--
作者：
Lu, Wenshu;Schneider, Maria;Karakesisoglou, Iakowos
Nesprs-1/-2/-3/-4是连接细胞核和细胞骨架的核膜蛋白。最大的Nesprin-1/-2亚型(称为巨型)通过其N-末端肌动蛋白结合域(ABD)拴住F-肌动蛋白。然而，Nesprin-3缺乏ABD，而是与结合中间细丝的plectin联系在一起。Nesprint通过其C-末端Kash结构域整合到外核膜上。在这里，我们展示了Nesprin-1/-2 ABD与Nesprin-3在物理和功能上的相互作用。因此，Nesprin-1/-2巨型蛋白的两端在核表面都是整合的：通过C端的Kash结构域和N端的Abd-Nesprin-3结合。有趣的是，Nesprin-2 Abd或Kash结构域的过度表达会导致核面积增加。相反，Nesprin-2 Mini(包含Abd和Kash-结构域，但缺乏大量的Nesprin-2巨棒片段)表达产生较小的核。当Nesprin-3共表达或微丝解聚时，核收缩进一步增强。我们的发现表明，多变量的Nesprin与细胞骨架之间的相互作用形成了覆盖在外核膜上的晶格状丝状网络，这决定了核的大小。
Nesprins-1/-2/-3/-4 are nuclear envelope proteins, which connect nuclei to the cytoskeleton. The largest nesprin-1/-2 isoforms (termed giant) tether F-actin through their N-terminal actin binding domain (ABD). Nesprin-3, however, lacks an ABD and associates instead to plectin, which binds intermediate filaments. Nesprins are integrated into the outer nuclear membrane via their C-terminal KASH-domain. Here, we show that nesprin-1/-2 ABDs physically and functionally interact with nesprin-3. Thus, both ends of nesprin-1/-2 giant are integrated at the nuclear surface: via the C-terminal KASH-domain and the N-terminal ABD-nesprin-3 association. Interestingly, nesprin-2 ABD or KASH-domain overexpression leads to increased nuclear areas. Conversely, nesprin-2 mini (contains the ABD and KASH-domain but lacks the massive nesprin-2 giant rod segment) expression yields smaller nuclei. Nuclear shrinkage is further enhanced upon nesprin-3 co-expression or microfilament depolymerization. Our findings suggest that multivariate intermolecular nesprin interactions with the cytoskeleton form a lattice-like filamentous network covering the outer nuclear membrane, which determines nuclear size.